The field of the invention is nuclear magnetic resonance imaging methods and systems. More particularly, the invention relates to the enhancement of tumor contrast in NMR images.
Cancer is the leading cause of death among women aged 35 to 50 in the United States, and breast cancer is the most common malignancy in this age group. It is estimated that the average American woman run a 1 in 9 chance of developing breast cancer in her lifetime. The American Cancer Society projects that about 175,000 U.S. women will be diagnosed with breast cancer this year, and 44,500 will die from the disease. Although some controversy persists, it is generally agreed that early detection of breast cancer using X-ray mammography can significantly reduce morbidity. Unfortunately, conventional X-ray mammography often fails to detect breast cancer because of limited tissue contrast particularly in women with predominantly fibro-glandular breasts (often younger women) that are not easily penetrated by X-rays. A further draw-back of X-ray mammography is the presence of ionizing radiation which poses some health risk and is unacceptable to many patients.
Even if breast lesion is detected with X-ray mammography, it is often difficult to confirm that the lesion actually represents cancer because of overlap in mammographic appearance between malignant lesions and a variety of benign lesions including fibroadenomas, necrotic fat and post-operative scarring. Currently, surgical biopsy is the only accurate way to determine the malignant or benign basis of a mammographic finding, however many biopsies are performed on what turn out to be benign lesions. In the United States, the number of cancers diagnosed per number of surgical biopsies performed is only about 20%. This means that approximately 8 out of every 10 surgical biopsies performed on the basis of mammographic or other evidence are `unnecessary`. Once diagnosed, effective treatment of breast cancer requires accurate localization of breast lesions in order to spare as much normal breast tissue as possible. Conventional X-ray mammography does not provide complete three-dimensional visualization of the breast and is not always sufficient to confirm the presence of multiple lesions. Clearly, alternative breast imaging methods are required in addition to X-ray mammography in order to improve detection, diagnosis and treatment of breast cancer.
Nuclear magnetic resonance (NMR) imaging is a useful adjunct to conventional X-ray mammography. NMR provides multiplanar cross-sectional images with exquisite soft tissue contrast from any view without the ionizing radiation associated with X-ray imaging.
Any nucleus which possesses a magnetic moment attempts to align itself with the direction of the magnetic field in which it is located. In doing so, however, the nucleus precesses around this direction at a characteristic angular frequency (Larmor frequency) which is dependent on the strength of the magnetic field and on the properties of the specific nuclear species (the magnetogyric constant .gamma. of the nucleus). Nuclei which exhibit this phenomena are referred to herein as "spins".
When a substance such as human tissue is subjected to a uniform magnetic field (polarizing field B.sub.0), the individual magnetic moments of the spins in the tissue attempt to align with this polarizing field, but precess about it in random order at their characteristic Larmor frequency. A net magnetic moment M.sub.z produced in the direction of the polarizing field, but the randomly oriented magnetic components in the perpendicular, or transverse, plane (x-y plane) cancel one another. If, however, the substance, or tissue, is subjected to a magnetic field (excitation field B.sub.1) which is in the x-y plane and which is near the Larmor frequency, the net aligned moment, M.sub.z, may be rotated, or "tipped", into the x-y plane to produce a net transverse magnetic moment M.sub.t, which is rotating, or spinning, in the x-y plane at the Larmor frequency. The degree to which the net magnetic moment M.sub. z is tipped, and hence the magnitude of the net transverse magnetic moment M.sub.t depends primarily on the length of time and the magnitude of the applied excitation field B.sub.l.
The practical value of this phenomenon resides in the signal which is emitted by the excited spins after the excitation signal B.sub.l is terminated. In simple systems the excited spin induce an oscillating sine wave signal in a receiving coil. The frequency of this signal is the Larmor frequency, and its initial amplitude, A.sub.0, is determined by the magnitude of the transverse magnetic moment M.sub.t. The amplitude, A, of the emission signal decays in an exponential fashion with time, t: EQU A=A.sub.0 e.sup.-t/T.sup.*.sub.2
The decay constant 1/T.sup.*.sub.2 depends on the homogeneity of the magnetic filed and on T.sub.2, which is referred to as the "spin-spin relaxation" constant, or the "transverse relaxation constant. The T.sub.2 constant is inversely proportional to the exponential rate at which the aligned precession of the spins would dephase after removal of the excitation signal B.sub.1 in a perfectly homogeneous field.
Another important factor which contributes to the amplitude A of the NMR signal is referred to as the spin-lattice relaxation process which is characterized by the time constant T.sub.1. It describes the recovery of the net magnetic moment M to its equilibrium value along the axis of magnetic polarization (z). The T.sub.1 time constant is longer than T.sub.2, much longer in most substances of medical interest.
The NMR measurements of particular relevance to the present invention are called "pulsed NMR measurements." Such NMR measurements are divided into a period of RF excitation and a period of signal emission. Such measurements are performed in a cyclic manner in which the NMR measurement is repeated many times to accumulate different data during each cycle or to make the same measurement at different locations in the subject. A wide variety of preparative excitation techniques are known which involve the application of one or more RF excitation pulses (B.sub.1) of varying magnitude, duration, and direction. Such excitation pulses may have a narrow frequency spectrum (selective excitation pulse), or they may have a broad frequency spectrum (nonselective excitation pulse) which produces transverse magnetization M.sub.t over a range of resonant frequencies. The prior art is replete with excitation techniques that are designed to take advantage of particular NMR phenomena and which overcome particular problems in the NMR measurement process.
When utilizing NMR to produce images, a technique is employed to obtain NMR signals from specific locations in the subject. Typically, the region which is to be imaged (region of interest) is scanned by a sequence of NMR measurement cycles which vary according to the particular localization method being used. The resulting set of received NMR signals are digitized and processed to reconstruct the image using one of many well known reconstruction techniques. To perform such a scan, it is, of course, necessary to elicit NMR signals from specific locations in the subject. This is accomplished by employing magnetic fields (G.sub.x, G.sub.y, and G.sub.z) which have the same direction as the polarizing field B.sub.0, but which have a gradient along the respective x, y and z axes. By controlling the strength of these gradients during each NMR cycle, the spatial distribution of spin excitation can be controlled and the location of the resulting NMR signals can be identified.
The present invention will be described in detail with reference to a variant of the well known Fourier transform (FT) imaging technique, which is frequently referred to as "spin-warp". The spin-warp technique is discussed in an article entitled "Spin Warp NMR Imaging and Applications to Human Whole-Body Imaging" by W.A. Edelstein et al., Physics in Medicine and Biology, Vol. 25, pp. 751-756 (1980). It employs a variable amplitude phase encoding magnetic field gradient pulse prior to the acquisition of NMR spin-echo signals to phase encode spatial information in the direction of this gradient. In a two-dimensional implementation (2DFT), for example, spatial information is encoded in one direction by applying a phase encoding gradient (G.sub.y) along that direction, and then a spin-echo signal is acquired in the presence of a readout magnetic field gradient (G.sub.x) in a direction orthogonal to the phase encoding direction. The readout gradient present during the spin-echo acquisition encodes spatial information in the orthogonal direction. In a typical 2DFT pulse sequence, the magnitude of the phase encoding gradient pulse G.sub.y is incremented (.DELTA.G.sub.y) in the sequence of views that are acquired during the scan to produce a set of NMR data from which an entire image can be reconstructed.
Numerous strategies are employed to enhance the contrast of various tissues in medical images reconstructed from NMR data. Such strategies usually take advantage of the fact that different tissue types exhibit different T.sub.1 and/or T.sub.2 (and T.sub.2.sup.*) relaxation times. For example, to suppress the signal produced by fat tissues, it is common practice to precede the NMR pulse sequence with an inversion RF pulse followed by a recovery time (TI) as described by Bydder et al JCAT 3, 251-254 (1985). By judiciously selecting the recovery time TI, the spins in fat tissue produce little transverse magnetization in the subsequent NMR pulse sequence, and therefore, little signal in the acquired NMR data. As a result, the fat tissues appear less bright in the reconstructed image and other tissues dominate the image. Such fat suppression techniques are essential in the imaging of some organs such as the breast, which have a high fat content.
To diagnose many diseases it is necessary to provide medical images which contrast other tissue types. For example, in the imaging of the breast it is important to provide contrast between normal fibro-glandular tissue and breast tumors. This is particularly a problem in younger women with more glandular breasts on whom mammography is often inconclusive. One reason for this lack of contrast is that the T.sub.1 relaxation times of fibro-glandular tissue and tumor tissue are nearly the same and this parameter cannot, therefore, be used as a contrast enhancing mechanism as with fat. Contrast agents such as Gadolinium may be injected into the subject shortly before the scan to shorten the T.sub.1 of tumor cells and provide a contrast mechanism, but this is a costly, invasive procedure that cannot be used on all patients and the timing of the injection is critical if maximum contrast is to be achieved.
Spin locking is an NMR experiment in which the equilibrium magnetization established by the polarizing magnetic field is rotated by a 90.degree. RF excitation pulse into the transverse plane and "locked" by the application of a much weaker rf field. In the rotating frame of reference and in the absence of spatial encoding gradients, spins are subject to an effective rf field EQU H.sub.eff =.DELTA.z+H.sub.l y, (1)
where the resonance offset, .DELTA.=H.sub.0 -.omega./.gamma.. H.sub.o is the magnitude of the static polarizing magnetic field in the direction z, .gamma. is the gyromagnetic ratio, and H.sub.1 is the magnitude of the rf field in the direction y as shown in FIG. 3A. If the rf field is applied on resonance (.omega.=.omega..sub.0 =.gamma.H.sub.0), the magnetization in the rotating frame, M.sub.0, is perturbed only by the applied rf field, H.sub.1. The transverse magnetization remains in phase along the direction of H.sub.1 and relaxes with time constant T.sub.1.rho.. At the end of the locking interval, the magnetization relaxes as a normal free induction decay (FID) as shown in FIG. 3B. One of the difficulties in applying this experiment to an imaging scan is that the RF locking field requires high power when used with the large polarizing magnetic fields employed with NMR imaging systems. This is difficult to achieve and it exceeds the SAR limits imposed on human subjects.
The same type of experiment can also be performed off resonance (.DELTA.&gt;H.sub.1). During the application of the off-resonance field pulse, the equilibrium magnetization M.sub.0 relaxes along the effective field .DELTA. inclined by an angle .theta. to the transverse plane. The off-resonance technique measures a relaxation time, T.sub.1.rho..sup.off, which Contains contributions from both the rotating frame and laboratory frame spin-lattice relaxation time, T.sub.1.rho. and T.sub.1, respectively. This technique enables T.sub.1.rho. information to be obtained without the large rf field strengths required for spin locking on resonance. As described in articles by G.E. Santyr et al entitle "Spin Locking for Magnetic Resonance Imaging with Application to Human Breast," Magnetic Resonance In Medicine, 12, 25-37 (1989) and "Off Resonance Field Pulsing For Contrast Manipulation in MRI Application to Human Breast Tissues," Proceedings of the SMRM," San Francisco (1988), the T.sub.1.rho. spin-lattice relaxation time can be used to distinguish breast tumors from other breast tissues.